The surgical procedures currently used to treat local cartilage damage (focal lesions) are: microfracture (MFX), autologous chondrocyte implantation (ACI), and mesenchymal stem cell (MSC) implantation. Although these procedures produce healthy cartilage, 18% of MFX and 16% of ACI require re-operation because of cartilage calcification, while nearly all MSC treatments exhibit some extent of chondrocyte hypertrophy, which is the initial stage of calcification.
Chondrocyte hypertrophy, the cell terminal differentiation stage, as well as calcification in general, are the result of specific pathways, in particular of SMAD1/5/8 phosphorylation, a canonical BMP pathway. Recently, a small synthetic molecule, dorsomorphin, has been found to interfere with SMAD1/5/8 phosphorylation, thus inhibiting chondrocyte terminal differentiation.